Absence of integrin alpha 1 beta 1 in the mouse causes loss of feedback regulation of collagen synthesis in normal and wounded dermis

Integrin alpha 1 beta 1 is a collagen receptor predominantly found in mesen chymal tissues. Mice lacking this receptor are viable. We have previously s uggested that alpha 1 beta 1 might participate in the down-regulation of co llagen gene expression observed in cells suspended inside collagen gels. Th e results presented here demonstrate that integrin alpha 1 beta 1 acts as a feedback regulator of collagen synthesis both in vitro and in vivo. Firstl y, alpha 1 null animals show a higher rate of collagen synthesis in the der mis in vivo. Secondly, fibroblasts derived from alpha 1 null cutaneous woun ds show a reduced sensitivity to collagen gel induced downregulation of col lagen mRNA synthesis, as compared to their wild-type counterparts. An incre ase in collagenase synthesis is also seen in the alpha 1 null dermis and in collagen gel suspended fibroblasts. While dermal thickness is normal in th e alpha 1 null animals, an increase is seen in skin thickness of alpha 1 nu ll but not alpha 1 heterozygote animals on a background of collagenase resi stant collagen. Increased expression of both collagen and collagenase mRNA are seen in experimental granulation tissue in alpha 1 null animals, but th eir ultimate accumulation of collagen is normal, probably due to non alpha 1 dependent paracrine regulators of collagen turnover.